Study On Mechanism Of Application Of Classic Prescription Shenlingbaizhu Powder In Diabetic Nephropathy Based On Network Pharmacology

ObjectiveThe pharmacological mechanism of Shenling Baizhu Powder in the treatment of diabetic nephropathy was analyzed by network pharmacology,and the effective components,potential targets and signaling pathways of Shenling Baizhu Powder in the treatment of diabetic nephropathy were discussed.At the same time,the stability of the binding of effective active ingredients to key targets was verified by simulated molecular docking.MethodsThe active components of Shenling Baizhu Powder were searched by TCMSP database,and the effective active components were screened by ADME standard.The effective active components were matched with the corresponding molecular targets in Uniport database.The molecular targets of diabetic nephropathy were obtained by using GeneCards,OMIM,PharmGkb,TTD and DrugBank databases.The intersection of drug targets and disease targets was taken,and the obtained intersection targets were imported into the String database for PPI network analysis.KEGG and GO enrichment analysis was performed by Metascape database.Cytoscape software was used to screen the key targets of intersection targets.At the same time,the molecular structure of key molecular targets was downloaded from the PDB database,and the active 3D structure of active ingredients was downloaded from the PubChem database.Molecular docking of molecular targets and active ingredients is performed using Pymol,adt and Auto Dock tools.Finally,the analysis results were visualized by Pymol software.ResultsThere were 194 effective active ingredients and 97 molecular targets in Shenling Baizhu Powder,9056 molecular targets in diabetic nephropathy,and 93 molecular targets in Shenling Baizhu Powder and diabetic nephropathy.KEGG enrichment analysis obtained 139 signaling pathways.The top rankings include Pathways in cancer,PI3K-Akt signaling pathway,Chemical carcinogenesis-receptor activation,Lipid and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,Th17 cell differentiation,Platinum drug resistance,FoxO signaling pathway,etc.Most of these signaling pathways involve oxidative stress,inflammatory response,immune regulation,etc.The main biological processes involved in GO enrichment analysis are : cell response to nitrogen compounds,response to exogenous stimuli,circulatory system processes,regulation of mitotic cell cycle,cell response to cytokine stimulation,etc.The main molecular functions are : dopamine neurotransmitter receptor activity,protein domain specific binding,cytokine activity,protein phosphatase binding,etc.;in terms of cell components,molecular target formation : transcription regulator complex,cyclin-dependent protein kinase holoenzyme complex,membrane raft,endoplasmic reticulum cavity,transcription inhibitor complex,etc.Molecular docking showed that the effective active ingredients of nobiletin,luteolin,quercetin,acacetin,diosgenin and chalcone A were stably combined with the top TNF and TP53 in the core targets.ConclusionShenling Baizhu Powder mediates the activity of multiple signaling pathways of oxidative stress and inflammatory response through quercetin,nobiletin and luteolin in effective active ingredients,affects the function of molecular targets such as TNF,TP53 and STAT3,and regulates diabetic nephropathy in multiple ways and targets.